Molecular Targeting of Ultrasonographic Contrast Agent for Detection of Head and Neck Squamous Cell Carcinoma

Abstract

Objective To investigate the feasibility of ultrasonographic (US) imaging of head and neck cancer with targeted contrast agents both in vitro and in vivo. We hypothesize that conjugation of microbubble contrast agent to tumor-specific antibodies may improve US detection of head and neck squamous cell carcinoma (HNSCC). Design Preclinical blinded assessment of anti-EGFR and anti-CD147 microbubble contrast agents for US imaging of HNSCC. Setting Animal study. Subjects Immunodeficient mice. Intervention Injection of targeted microbubbles. Main Outcome Measure Microbubble uptake in tumors as detected by US. Results In vitro assessment of anti–epidermal growth factor receptor (EGFR) and anti-CD147–targeted micro-bubbles in 6 head and neck cancer cell lines yielded a 6-fold improvement over normal dermal fibroblasts (P<.001). Binding of targeted agents had a positive correlation to both epidermal growth factor receptor (EGFR) (R2=0.81) and CD147 (R2=0.72) expression among all cell lines. In vivo imaging of flank tumors in nude mice (N=8) yielded enhanced resolution of anti-EGFR– and anti-CD147–targeted microbubble agents over IgG control (P<.001), while dual-targeted contrast agents offered enhanced imaging over single-targeted contrast agents (P=.02 and P=.05, respectively). In a blinded in vivo assessment, targeted contrast agents increased intratumoral enhancement of flank tumors over controls. Targeted US contrast agents to both EGFR and CD147 were 100% sensitive and 87% specific in the detection of flank tumors. Conclusion This preclinical study demonstrates feasibility of using molecular US to target HNSCC for contrast-enhanced imaging of HNSCC tumor in vivo.

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

“…In a preclinical setting Targestar-B was targeted to epidermal growth factor receptor (EGFR) and CD147 expressed in head and neck squamous cell carcinoma, where using the dual targeting was reported as most promising [47]. Although Eselectin is not a novel target, its up-regulation due to inflammation can also be used to monitor tumour progression and metastasis.…”

Recent developments in dynamic contrast-enhanced ultrasound imaging of tumor angiogenesis

“…Results from this study revealed a 2.1- and 1.5-fold increase in the mean molecular US signal when using dual-targeted MBs versus the VEGFR2 and α V β 3 integrin-targeted MBs, respectively. Similar molecular US image enhancement patterns were observed when using a dual-targeted MB to both EGF receptor and extracellular matrix metalloproteinase inducer (CD147) compared with the single-targeted MB strategies [104]. As shown by Warram et al , multitargeted MBs produce a synergistic effect when used for molecular US imaging of tumor angiogenesis [91].…”

Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

“…Future work should continue the development and validation of clinically translatable highresolution DCE-US imaging methods for more accurately quantifying tumor angiogenic biomarkers throughout an entire tumor mass. Actively targeting the MB contrast agents to tumor neovascularity and over-expressed biomarkers may also help improve angiogenic biomarker quantification given enhanced visualization of the tumor neovascular network [19][20][21][22][23][24].…”